The involvement of PARP in the development of complications of diabetes, including neuropathy, nephropathy, retinopathy and in vascular complications, has been demonstrated in various preclinical models. The use of PARP inhibitors appears to ameliorate these complications via conservation of cellular energy pools and prevention of the up-regulation of various pro-inflammatory pathways (Kern et al., Exp Diabetes Res 2007). Furthermore, recent work has suggested that an Inotek PARP inhibitor has anti-angiogenic activity that may be advantageous in preventing the later proliferative stages of diabetic retinopathy (Pyriochou et al., Int J Mol Med 2008).
Preclinical work conducted with an Inotek PARP inhibitor demonstrated in a diabetic rodent model that PARP inhibition protected against both the death of retinal blood vessel cells and what are considered hallmark lesions of diabetic retinopathy, including acellular capillaries and pericyte ghosts in the retinal vasculature (Zheng et al., Diabetes 2004).